It has been known that angiogenesis has a great influence on wound healing and progression of many diseases. As ophthalmologic diseases with which angiogenesis is associated, retinopathy of prematurity, diabetic retinopathy, wet age-related macular degeneration, neovascular glaucoma, neovascular maculopathy, and the like have been known. Moreover, corneal neovascularization caused by various stimuli given to cornea or invasion therein has also been known. In these diseases, a control mechanism-lacked angiogenesis has occurred. A vascular endothelial growth factor (VEGF) is associated with such angiogenesis. Examples of a known anti-VEGF drug may include Bevacizumab as an anti-VEGF antibody, Sorafenib, Sunitinib, Pegaptanib sodium, Ranibizumab, Aflibercept, and VEGF-Trap EYE. Medicaments that target VEGF have been widely used in clinical sites for the treatment of eye diseases such as age-related macular degeneration, branch retinal vein occlusion, central retinal vein occlusion, diabetic maculopathy, diabetic retinopathy, and neovascular glaucoma. However, VEGF has various actions, such as the maintenance of homeostasis of normal retinochoroidal vessels (see, for example, Non Patent Literature 1) and action as a nutritional factor for retinal neurons (see, for example, Non Patent Literature 2).
On the other hand, with regard to a pyrazolone derivative represented by the following formula (I):
wherein R1 represents a hydrogen atom, aryl, C1-5 alkyl, or C3-6 (total carbon number) alkoxycarbonylalkyl, R2 represents a hydrogen atom, aryloxy, arylmercapto, C1-5 alkyl, or C1-3 hydroxyalkyl, or R1 and R2 are combined with each other to represent C3-5 alkylene, and R3 represents a hydrogen atom, C1-5 alkyl, C5-7 cycloalkyl, C1-3 hydroxyalkyl, benzyl, naphthyl or phenyl, or phenyl substituted with the same or different 1 to 3 substituents selected from the group consisting of C1-5 alkoxy, C1-3 hydroxyalkyl, C2-5 (total carbon number) alkoxycarbonyl, C1-3 alkylmercapto, C1-4 alkylamino, C2-8 (total carbon number) dialkylamino, a halogen atom, trifluoromethyl, carboxyl, cyano, a hydroxyl group, nitro, amino, and acetamide, it has been known that this pyrazolone derivative has, as intended use of a medicament, brain function-normalizing action (Patent Literature 1), lipid peroxide generation-inhibiting action (Patent Literature 2), eye cloudiness-inhibiting action (Patent Literature 3), action to inhibit retinal neurodegeneration (Patent Literature 4), and action to inhibit progression of atrophic age-related macular degeneration (Non Patent Literature 3). However, these publications neither suggest nor teach the effectiveness of this compound as a therapeutic agent or a preventive agent for ophthalmologic diseases caused by ocular angiogenesis.